Patients with intermediate-risk acute myeloid leukemia (AML) who underwent allogeneic hematopoietic cell transplantation (HCT) after their first complete remission showed improvements in disease-free survival but had similar overall survival rates compared with patients treated with consolidation chemotherapy alone.
Notably, all patients who relapsed after consolidation chemotherapy were able to receive allogeneic HCT, suggesting that transplantation may be safely delayed in some patients until their first relapse.
“The results of this randomized clinical trial indicate that the probability of survival after [allogeneic] HCT is not superior to that of conventional consolidation chemotherapy” among patients 60 years or younger with intermediate-risk AML, the authors conclude.
However, two experts highlighted several caveats to the study, which suggest the results may not translate to current clinical practice.
The study was published online last week in JAMA Oncology.
Approximately 50%-70% of patients with AML who receive intensive induction chemotherapy for AML and achieve a first complete remission are referred for post-remission therapy.
While consolidation chemotherapy with high-dose cytarabine has shown a benefit for those with a favorable risk profile, patients considered high-risk with adequate performance status may be candidates for allogeneic HCT.
However, determining the optimal post-remission treatment option for patients who fall into the intermediate-risk category can be more challenging.
To compare outcomes among intermediate-risk patients, researchers from Germany conducted a multicenter trial, enrolling 143 adults aged 60 or younger with intermediate-risk AML who had achieved first complete remission or complete remission with incomplete blood cell count recovery following conventional induction therapy.
The patients, who had a mean age of 48.2 years, were randomly assigned to consolidation treatment with allogeneic HCT (n = 76) or chemotherapy with high-dose cytarabine (n = 67), with the option for salvage HCT in the case of relapse. Overall, 12 patients in the HCT group received one consolidation course of high-dose cytarabine after achieving complete remission to bridge until allogeneic HCT, while all other patients in this group received allogeneic HCT directly after induction therapy.
Overall, disease-free survival at 2 years was significantly higher in the allogeneic HCT group (69%) compared with the consolidation therapy group (40%; P = .001). And the cumulative incidence of relapse at 2 years in the allogeneic HCT group was also lower, at 20% compared with 58% in the consolidation therapy group (P < .001).
The overall survival data, however, painted a slightly more complex picture. In the intention-to-treat analysis, the probability of survival at 2 years was similar between the allogeneic HCT group (74%, or 56 of 76 patients) compared with consolidation chemotherapy (84%, or 56 of 67 patients; P = .22).
In addition, the rates of nonrelapse mortality at 2 years were higher in the allogeneic HCT group (9%) vs chemotherapy (2%; P = .005).
Although the rate of nonrelapse mortality was higher with allogeneic HCT, the relatively low rate with each treatment strategies was “an important and rewarding finding,” the authors noted. “This achievement is clearly due to the availability of less toxic but still effective conditioning therapies and modern antiviral and antifungal prophylaxis.”
In addition, among the 41 patients who relapsed after consolidation chemotherapy, all received allogeneic HCT, and the authors observed no significant differences between the groups in terms of health-related quality of life measures.
Results “ May Not Translate to Real-Life Clinical Practice”
An important caveat is the findings do not reflect some key updated strategies currently used in clinical practice, said Diego Adrianzen Herrera, MD, from the University of Vermont’s Larner College of Medicine in Burlington, who was not involved in the study.
“A charitable interpretation of the results is that a clear, large survival benefit of transplant in first complete remission is not apparent, which in turn can inform decision-making in certain circumstances for patients meeting the trial criteria, [including] younger patients with a readily available donor,” he told Medscape Medical News.
“However, risk stratification strategies currently used were not followed,” he said.
For instance, molecular risk stratification was not universally used, which may have led the researchers to overrepresent the number of patients considered to have favorable risk disease and “could have skewed the results in favor of the chemotherapy arm,” he explained.
In addition, minimal residual disease surveillance by flow cytometry was not used. Plus, Herrera added, in practice, not all patients can be salvaged and taken to HCT when in their second complete remission, or even achieve complete remission again.
“Unfortunately, these issues make the clinical significance of these results limited,” he concluded.
Margaret Kasner, MD, who was not associated with the research, agreed that aspects of the study design may not translate to real-life clinical practice, particularly in terms of quality-of-life outcomes.
“Although the [study] showed no difference in quality of life in the patient groups, this is likely due to the patient selection,” Kasner, of the Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, told Medscape Medical News. “Most patients do not allow themselves to be randomized between these two very different strategies, so those who are willing to be randomized may be a different population in terms how their quality of life is affected by relapse.”
The authors acknowledged some of these limitations, adding that the routine use of minimal residual disease monitoring in some patients was only established once the trial was underway, and the number of patients with complete minimal residual disease was therefore limited.
In addition, Herrera explained that because HCT involves significant disruptions to daily life and extensive follow-up and monitoring, decisions to use the strategy are not taken lightly by clinicians or patients.
“This is a major issue,” he said. “HCT remains a therapeutic option which causes significant apprehension to patients.”
Nevertheless, “in my experience most patients would prefer an upfront strategy if there is a definitive need for transplant,” he added. “I think the main question patients have is whether they absolutely need an HCT and how can we better identify up front who will be in the relapse-free group at 2 years.”
The study received grant funding from the Deutsche Forschungsgemeinschaft. The authors’ disclosures are detailed in the original article. Herrera and Kasner report no relevant financial relationships.
JAMA Oncology. Published online February 9, 2023. Abstract
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